A Study of Filanesib (ARRY-520) and Carfilzomib in Patients With Advanced Multiple Myeloma

• Drug: Carfilzomib, proteasome inhibitor; intravenous
  multiple dose, single schedule
• Drug: Filanesib, KSP(Eg5) inhibitor; intravenous
  multiple dose, single schedule
• Drug: Dexamethasone, steroid; oral or intravenous
  as indicated, per the carfilzomib prescribing information
• Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous
  standard of care

• Experimental: Carfilzomib + Filanesib

  Single agent + Carfilzomib arm.

  Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information.

  Filgrastim to be administered per the approved product prescribing information and institutional guidelines.

  Interventions:

  • Drug: Carfilzomib, proteasome inhibitor; intravenous
  • Drug: Filanesib, KSP(Eg5) inhibitor; intravenous
  • Drug: Dexamethasone, steroid; oral or intravenous
  • Drug: Filgrastim, granulocyte-colony stimulating factor (G-CSF); subcutaneous
• Experimental: Carfilzomib

  Single agent arm.

  Patients will be hydrated prior to and following carfilzomib administration and will be premedicated with dexamethasone, per the carfilzomib prescribing information.

  Interventions:

  • Drug: Carfilzomib, proteasome inhibitor; intravenous
  • Drug: Dexamethasone, steroid; oral or intravenous

Key Inclusion Criteria:

• Confirmed multiple myeloma with measurable disease.
• Disease refractory to last myeloma regimen.
• Patients must have received at least 2 prior treatment regimens, including bortezomib and an IMiD (e.g., lenalidomide, thalidomide, pomalidomide). Induction therapy and stem cell transplant ± maintenance are to be considered as a single regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to first dose of study treatment.
• Adequate hematology, liver and renal function laboratory values within 14 days prior to first dose of study treatment.
• Additional criteria exist.

Key Exclusion Criteria:

• Prior treatment with carfilzomib, filanesib, or any other KSP inhibitor.
• Past or current plasma cell leukemia.
• Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).
• Ongoing Grade 3 or Grade 4 peripheral neuropathy, or Grade 2 peripheral neuropathy with pain despite appropriate interventions, within 28 days prior to first dose of study treatment.
• Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study treatment.
• Concomitant malignancies or previous malignancies (other than multiple myeloma) with less than a 2-year disease-free interval at the time of first dose of study treatment. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or Stage 1 prostate cancer are eligible irrespective of the time of diagnosis.
• Known pulmonary hypertension of any severity.
• Concurrent cardiac disease that, in the judgment of the Investigator, would make the patient inappropriate for study participation.
• Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C.
• Acute active infection requiring treatment.
• Additional criteria exist.